Abstract
Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10−6, experiment-wide significant), as well as OFCC1 (P=6.29 × 10−5). The suggestive findings in this study await replication in larger samples.
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Acknowledgements
The OCD Collaborative Genetics Association Study (OCGAS) is a collaborative research study and was funded by the following NIMH Grant Numbers: MH071507, MH079489, MH079487, MH079488 and MH079494. Y-YS and H-DQ were also supported by the Intramural Research Program of the NIMH. We thank the families who have participated in the study; David Houseman, PhD, Kathleen Merikangas, PhD, and Alec Wilson, PhD, for consultation; and the clinicians, study managers and clinical interviewers at the respective study sites for their efforts in participant recruitment and clinical assessments: Columbia University: Blair Simpson, MD, PhD, Julianna Stevens, BA Katie Buchholz; Johns Hopkins University: Graham Redgrave, MD, Krista Vermillion, BA, Janice Krasnow, PhD, Jana Drew, PhD, Melissa Meyers, PhD, and Margaret Schlossberg, PhD; Harvard/Massachusetts General Hospital: Elizabeth Mancuso, BA, Alyssa Faro, BA, Ashley Brown, BA, Kesley Ramsay, BA; National Institute of Mental Health (NIMH): Theresa B DeGuzman.
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Mattheisen, M., Samuels, J., Wang, Y. et al. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 20, 337–344 (2015). https://doi.org/10.1038/mp.2014.43
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DOI: https://doi.org/10.1038/mp.2014.43
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